6-32038423-A-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000500.9(CYP21A2):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_000500.9 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP21A2 | NM_000500.9 | c.1A>G | p.Met1? | start_lost | Exon 1 of 10 | ENST00000644719.2 | NP_000491.4 | |
CYP21A2 | NM_001128590.4 | c.1A>G | p.Met1? | start_lost | Exon 1 of 9 | NP_001122062.3 | ||
CYP21A2 | NM_001368143.2 | c.-424A>G | 5_prime_UTR_variant | Exon 1 of 10 | NP_001355072.1 | |||
CYP21A2 | NM_001368144.2 | c.-334A>G | 5_prime_UTR_variant | Exon 1 of 9 | NP_001355073.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
This sequence change affects the initiator methionine of the CYP21A2 mRNA. The next in-frame methionine is located at codon 82. The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. Disruption of the initiator codon has been observed in individuals with classic salt-wasting, simple virilizing and non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (PMID: 14676460, 23142378, 25227725, 31006099). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.